The principal objective of this study is to develop methodologies in the rat for identifying sedatives, hypnotics and anxiolytic drugs which have a lower capacity to produce tolerance and dependence as well as toxicity as a consequence of interactions with other drugs. Behavioral, autonomic and motor signs will be observed in nondependent and both stabilized and abstinent dependent rats. Pharmacologic profiles and quantitative scales measuring depression and abstinence will be developed. By obtaining dose response curves which will allow the quantitative estimates of the degrees of tolerance and cross tolerance, dependence and cross dependence as well as interaction toxicity, it will be possible to make inferences about possible receptor kinetics. The configurations of the dose response will provide evidence about the agonistic and partial agonistic actions of these types of drugs. The pharmacologic profiles, with an associated sign analysis, may provide leads about differences in selectivity and modes of action. The prototypic drugs which will first be investigated are alcohol, chloral hydrate, secobarbital, pentobarbital, methaqualone, chlordiazepoxide and diazepam. A method using a gastric fistula will be developed for administering drugs, particularly insoluble one, safely and chronically.